CN101686933A - Membrane shell of an implantable dosage system - Google Patents
Membrane shell of an implantable dosage system Download PDFInfo
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- CN101686933A CN101686933A CN200880022411A CN200880022411A CN101686933A CN 101686933 A CN101686933 A CN 101686933A CN 200880022411 A CN200880022411 A CN 200880022411A CN 200880022411 A CN200880022411 A CN 200880022411A CN 101686933 A CN101686933 A CN 101686933A
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- putamina
- implant
- closure
- chamber
- groove
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- 239000012528 membrane Substances 0.000 title abstract description 14
- 239000007943 implant Substances 0.000 claims description 74
- 239000003795 chemical substances by application Substances 0.000 claims description 49
- 230000003213 activating effect Effects 0.000 claims description 48
- 238000001746 injection moulding Methods 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 12
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 12
- 238000012377 drug delivery Methods 0.000 claims description 11
- -1 polydimethylsiloxane Polymers 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 abstract description 8
- 239000013543 active substance Substances 0.000 abstract 1
- 239000011257 shell material Substances 0.000 description 36
- 239000003814 drug Substances 0.000 description 19
- 239000000463 material Substances 0.000 description 13
- 239000011159 matrix material Substances 0.000 description 13
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 11
- 239000000806 elastomer Substances 0.000 description 8
- 229920001971 elastomer Polymers 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 8
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 238000004132 cross linking Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000012867 bioactive agent Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000012190 activator Substances 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 125000005702 oxyalkylene group Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000003618 dip coating Methods 0.000 description 1
- 230000005520 electrodynamics Effects 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Polymers C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Prostheses (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The membrane shell of an implantable dosage system according to the invention is particularly suitable for subcutaneous applications to release an active agent with steady amounts during a longer period of time. The membrane shell (3) according to the invention comprises a first half (1) and a second half (2), which both halves comprise a continuous closure edge (8, 9), and are adapted to be connected to each other through a closable joint. The closure edges (8, 9) of the halves comprise at least one groove (10) and/or at least one protrusion (11) as continuous or discontinuous, and the membrane shell (3) is adapted to be closed so that at least one protrusion (11) and/or at least one groove (10) of the second half becomes opposed to at least one groove (10) and/or at least one protrusion(11) of the first half through a snap-fit joint.
Description
Technical field
The present invention relates to the putamina (membrane shell) of the drug-supplying system (dosage system) of activating agent, be specifically related to be used for subcutaneous application and in the long period with the putamina of the drug-supplying system of amount (steady amount) release bioactive agent stably.More specifically, the present invention relates to contain the putamina of closable joint (closablejoint).The invention still further relates to implantable drug delivery system (implantable dosage system) or implant (implant), described implantable drug delivery system or implant comprise according to putamina of the present invention and are embedded in the described putamina and contain one or more nuclear cores (core) of activating agent.
Background technology
Be used for subcutaneous application and in the given period with given speed most preferably so that the drug-supplying system or the implant of speed release bioactive agent can be divided into four groups substantially stably.
In matrix type implant (matrix-type implant), activating agent is dispersed in the carrier material matrix.Described carrier mass can be porous or non-porous solid or porous or non-porous semisolid, and described carrier mass can see through activating agent or not see through activating agent.The matrix type implant can be biodegradable, makes them will slowly degrade after administration stops.On the other hand, nondegradable matrix type implant comes release bioactive agent by diffusion through the wall or the hole of described substrate.The matrix type implant is easy to make, but they can not be used to send some activating agent.The problem of matrix type implant is to realize rate of release (zero order kinetics) stably, and this is because rate of release depends on the concentration of activating agent in substrate usually.
Nuclear core pattern implant (core-type implant) comprises nuclear core/chamber (bank) that contains activating agent and the film (rate controlling membranes (rate controllingmembrane, rcm)) that centers on described nuclear core/chamber and sustained release speed.Described film can be a porous or non-porous, but it is not biodegradable usually.The rate of release of nuclear core pattern implant is easier to keep constant usually, and this is because rate of release only mainly depends on the surface area of film.
The 3rd group is the so-called implant (hybrid implant) that mixes, and it contains matrix core in the rate controlling membranes inboard.
Other drug delivery system can be in itself machinery and contain small electrodynamic pump or the osmotic pumps that medicine is housed.Be easy to realize release stably with this class device, but they are very expensive, therefore can not compete with matrix type implant and nuclear core pattern implant.
Open text GB 1,157,370 has disclosed the implant of subcutaneous use, and this implant is made up of porous (sieve sample) top layer, porous (sieve sample) bottom, the thick relatively inertia internal layer and the annular sidewall that are used for tablet (drug pellet).The shell of described implant can followingly be made: for example be two independent parts with polyethylene molding or be molded as by hinge two parts connected to one another.This solution is characterised in that very the structure of complexity is made up of many independent parts, and the assembling of described implant becomes and requires great effort very much and difficulty thus.
Open text EP 1100669 has disclosed the implantable drug delivery system that makes by injection moulding.According to the disclosure text, can limit the shape of implant according to purpose, mentioned ring-type or bar-shaped implant particularly.Nuclear core in shell or film inboard can be a solution basically, and perhaps it can contain air, and perhaps it can be the solution suspension of activating agent or the powder type of activating agent.In this manufacturing technology, during the manufacturing of putamina, medicine is bonded in the implant.
At the activator administration system that is used for subcutaneous purposes according to prior art, in most of the cases determining amount and the intensity of activating agent with regard to product needed in the manufacture process at final products before the manufacturing of final products or at the latest.For example, in nuclear core pattern solution, the nuclear core that perhaps will contain activating agent during the manufacturing of putamina is combined in the film inboard, perhaps afterwards by using for example dip-coating to form shell on the nuclear core.
Contain film and be generally bar-shaped or cyclic, in these implants, perhaps activating agent is bonded in the implant equally, perhaps on completed nuclear core, formed shell afterwards with extruding simultaneously of film based on the implant of extruding technology.
Although having the implant of different shape and size with different technology manufacturings is known, but the problem that exists is, the implant with the particular form preparation that is used for specific purposes strictly is limited to certain pattern and certain way activating agent is embedded in the film inboard.Should advantageously the putamina with same structure/shape can be used for various purposes and also for example form and intensity according to using the activating agent of determining needs in light of the circumstances.
Summary of the invention
The present invention relates to the putamina of implantable drug delivery system, described putamina comprises first half-sum the second half, these two halves all comprise inner surface and outer surface, make these two halves be suitable for being connected to each other by closable joint, described closable joint comprises the first half successive closure edge (closure edge), described the first half successive closure edge is on the first half inner surface, it is basically in the periphery of the first half inner surface, with the second half successive closure edge, described the second half successive closure edge is on the second half inner surface, it is basically in the periphery of the second half inner surface, and the closure edge of these two halves comprises at least one groove (groove) and/or at least one projection (protrusion), described at least one groove and/or at least one projection are continuous or discontinuous, and described putamina is suitable for closure, makes at least one projection of described the second half and/or at least one groove at least one groove and/or at least one projection offset (oppose) by snap-fit joint (snap-fit joint) and described the first half.
According to a kind of embodiment, comprise continuous recess according to the first half closure edge of putamina of the present invention, and the second half closure edge comprises successive projection.
Can be connected to each other by film hinge (membrane hinge) according to first half-sum of putamina of the present invention the second half.
Described putamina can preferably be made by the polydimethylsiloxane with injection moulding quality (polydimethylsiloxane of injection moulding quality).
Two halves according to putamina of the present invention also comprise at least one hole, chamber (cavity pit) or hole (pit) except described closure edge, hole, described chamber or hole are on the first half inner surface and/or the second half inner surface, and it is basically at the middle part of the first half inner surface and/or the second half inner surface.According to a kind of embodiment, when closed membrane shell makes inner surface toward each other, at least one hole, chamber of described the first half be suitable for at least one hole, chamber of described the second half in opposite directions.
The invention still further relates to implantable drug delivery system or implant, described implantable drug delivery system or implant comprise according to putamina of the present invention and contain activating agent and be suitable for being bonded to one or more nuclear cores at least one chamber of putamina inboard (cavity).
Can by snap-fit joint with the shell closure before, one or more in type nuclear cores are bonded in the hole, one or more chambeies of putamina.Selectively, one or more nuclear cores can be injected at least one chamber of closed membrane shell inboard.
The putamina that contains closable joint according to the present invention makes the medicine can be in every way and with the multi-form implant inboard that is embedded in.In this way, for example can influence the release of medicine.Activating agent is added into the dosage, state and the intensity that make described activating agent in the completed putamina can be determined after the manufacturing of the implant shell of reality in light of the circumstances.Employed form influences in the putamina although the rate of release of the thickness of putamina and surface area effect activating agent (release rate), rate of release also can partly be subjected to activating agent is bonded to.
Injection molding technology is molding freely, thereby can be according to the object choice shape of treatment.
Be known that activating agent is not all to work when using with various cross-linking systems.Implant according to the present invention makes the nuclear core that contains activating agent can have the cross-linking system different with film to become possibility.Therefore, the cross-linking system that the cross-linking system that uses in putamina is not suitable for activating agent limits.
Description of drawings
Fig. 1. Fig. 1 a illustrate overlook observation before closure according to the putamina of implant of the present invention and its section A-A.
Fig. 1 b illustrates the cross section of the putamina that is arrangement for closed configuration.
Fig. 2. Fig. 2 illustrates and is the profile according to the putamina of implant of the present invention of opening form (Fig. 2 is a) and be the profile (Fig. 2 b) according to the putamina of implant of the present invention of arrangement for closed configuration.
The specific embodiment
The activator administration system that is used for the activating agent implant of subcutaneous purposes among the application or is used for subcutaneous purposes is meant putamina and contains the formed complex of nuclear core of activating agent.
Activating agent or effectively agent be meant and be suitable for the material that uses at the implant that is used for the mankind or animal, the effect of desirable medical effect or effect or some other kinds or the medicine or the hormone of effect for example are provided.
According to the putamina of implantable drug delivery of the present invention system by injection moulding by the plastic material manufacturing that is suitable for application target.Can use multiple thermosetting plastics.Preferable material is an elastomer, for example Organosiliconcopolymere.Be used for the especially preferred material that putamina according to the present invention uses be polydimethylsiloxane (polydimethyl siloxane, PDMS).
Fig. 1 a and 1b illustrate the putamina (3) according to implantable drug delivery of the present invention system, and described putamina (3) comprises the first half (1) and the second half (2).Use is columned according to the implant of the putamina manufacturing of Fig. 1 a and 1b, makes that the horizontal cross-section of cylinder is circle and height (being the thickness of implant) cylinder is constant in whole cross section everywhere (over the entire cross-sectional surface) basically.Described two halves (1,2) can be connected to each other by film hinge (12), in this way, described different two halves will be kept preferably and connect, this especially will help the alignment of described two halves when closed membrane shell, in addition, this also will keep being connected to each other by the part that makes coupling helping described small items is operated.Yet film hinge (12) is optional, and can before settling implant the putamina (3) of film hinge (12) from closure be removed.
The first half (1) comprise outer surface (4), and described outer surface (4) is meant when putamina is arrangement for closed configuration observable the first half surface.The first half outer surface (4) limits by the first half outward flange (13), and described outward flange (13) is meant the point in the first half edge, and when shell (3) when being arrangement for closed configuration, the first half (1) and the second half (2) contact with each other at described some place.
The first half also comprise inner surface (5), and described inner surface (5) is meant when putamina is arrangement for closed configuration on inboard invisible the first half (1) the surface of putamina (3).The first half (1) inner surface (5) limits by the first half outward flange (13).On the first half inner surface,, there is the first half hole, chamber (18) basically at its middle part.The first half hole (18) is formed on first side in the inboard chamber (17) that produces of putamina.The first half hole limits by the first half inward flange (14).
Inner surface (5) the first half (1) is gone up and is existed the first half closure edge (8), described closure edge (8) to comprise the zone that extends to the first half inward flange (14) from the first half outward flange (13).The width of the first half closure edge equals the distance of outward flange (13) to inward flange (14).In Fig. 1, between outward flange (13) the first half and the first half the inward flange (14), perhaps in the zone of the first half closure edge (8), there is continuous recess (10).The groove (10) of the first half closure edge (8) has the cross section profile that certain cross section profile is a groove.
Correspondingly, the second half (2) comprise outer surface (6), and described outer surface (6) is meant when putamina is arrangement for closed configuration observable the second half surface.The second half outer surface (6) limits by the second half outward flange (15), and described outward flange (15) is meant the point in the second half edge, and when shell was arrangement for closed configuration, the first half (1) and the second half (2) contacted with each other at described some place.
The second half (2) also comprise inner surface (7), and described inner surface (7) is meant when putamina is arrangement for closed configuration on invisible the second half inboard surface of putamina (3).The second half (2) inner surface (7) limits by the second half outward flange (15).On the second half inner surface (7),, there is the second half hole, chamber (19) basically at its middle part.The second half hole (19) is formed on second side in the inboard chamber (17) that produces of putamina (3).The second half (2) hole (19) limits by the second half inward flange (16).
Inner surface (7) the second half is gone up and is existed the second half closure edge (9), described closure edge (9) to comprise the zone that extends to the second half inward flange (16) from the second half outward flange (15).The width of the second half closure edge equals the distance of outward flange (15) to inward flange (16).In Fig. 1, between outward flange (15) the second half and the second half the inward flange (16), perhaps in the zone of the second half closure edge (9), there is successive projection.The continuous projection (11) of the second half closure edge (9) has the i.e. cross section profile of projection of certain cross section profile.
According to Fig. 1 b, be connected to each other when making inner surface toward each other by closable joint when the first half (1) and the second half (2), form the chamber (17) in putamina (3) and the putamina (3).Closable joint (being also referred to as snap-fit joint in this application) is meant the complex that the continuous closure edge (9) by the first half continuous closure edge (8) and the second half forms.According to the embodiment shown in Fig. 1 a and the 1b, the inner surface by arranging the first half inner surface and the second half makes the second half continuous projection and the first half continuous groove offset toward each other, thereby with the putamina closure.With regard to the tight closure of putamina according to the present invention (3), importantly, the first half closure edge and the second half closure edge is offseted, make projection closely place groove.
Closable joint according to the present invention shown in Fig. 1 a and the 1b comprises the first half continuous closure edge, described the first half continuous closure edge comprises continuous recess, with the second half continuous closure edge, described the second half continuous closure edge comprises successive projection.According to the present invention, the groove and the projection of closure edge also can be set otherwise, be that putamina comprises closable joint and do not break away from basic design of the present invention.Closure edge also can comprise the flat site of no any groove or projection except groove and/or projection.In the flat site of closure edge, the inner surface of described two halves offsets under the situation of no snap-fit joint each other.Should limit ratio and the layout of this flat site in closure edge, make the enough joints of maintenance between described two halves.
For example, the first half groove can be discontinuous, and the second half projection will correspondingly be discontinuous thus, make when the inner surface of the described two halves of arrangement toward each other the time the first half groove and the second half projection will become and offset.Discontinuous among the application is meant that the closure edge of arranging along the periphery of shell half (membrane shellhalf) comprises the discrete groove with certain-length or the discrete projection with certain-length continuously and between the described groove or the flat site between described projection, makes closure edge become basically along the continuum that the whole periphery of described shell half is extended.
Closable joint also can be a cogwheel type (cogwheel-type), and the first half continuous closure edge alternately comprises projection and groove with certain cycle thus.Correspondingly, the second half continuous closure edge will alternately comprise groove and projection with certain cycle.Described two halves are arranged to inner surface toward each other, make half the projection of winning place the second half groove, and on the other hand, make the second half projection place the first half groove, form according to closable joint of the present invention this moment.Continuous recess and the number of projection in the closure edge zone can be determined in light of the circumstances.
In the above-described embodiment, described projection and groove are set, make that the frequency with 1 time/unit length comprises single groove or single projection to closure edge in horizontal (lateral direction) last (in the zone with regard to Fig. 1 between described half inward flange and outward flange).
According to the present invention, described closure edge also can be in transversely comprising of closure edge (side by side) arranged side by side a plurality of (for example two) groove and/or projection.Described groove and/or projection can be side by side along whole length of closure edge or only arrange along the partial-length of closure edge.Groove of arranging side by side and/or number of protrusions are subjected to following true the restriction: on the one hand, the size of implant can not ad infinitum increase, and on the other hand, should keep enough spaces for the nuclear core that contains activating agent.
Except above-mentioned selectable closure edge, the layout of projection and/or groove and/or flat site other type in the closure edge zone also can be expected.For the present invention importantly, one or more grooves of the first half of described putamina and/or one or more projection and the second half one or more projectioies and/or one or more groove offset, and this causes described two halves closely to connect by snap-fit joint.According to the present invention, closable joint is located substantially on described half edge or periphery.
Fig. 1 illustrates the most preferred embodiment of the present invention about closable joint.In this most preferred embodiment, closable joint comprises the first half the continuous closure edge that contains continuous groove and the second half the continuous closure edge that contains continuous projection.
At least one projection of closable joint and the cross section profile of groove can be any cross section profiles that is suitable for application target.For example, it can have so-called dovetail profile (dovetail profile), and some broadens its protrusions (convex), and groove (spill) is correspondingly broadening on the direction of bottom portion of groove.
Principle well known by persons skilled in the art is followed in design/typing (design/sizing) that protruding and groove carry out, and described principle is relevant with injection molding technology on the one hand, and relevant with the function of closable joint on the other hand.What must consider with regard to injection molding technology is, for example the second half projection must and mold separation, perhaps contrary tapering (reverse taper) (negative angle (negative angle)) is necessarily not too big.In the design of closable joint, the most basic is that described two halves are connected to each other by the junction surface.
The term snap-fit joint that is used for closable joint among the application not necessarily is meant the title according to described junction surface, when projection and groove offset when making that described two halves are connected to each other, should hear any patter sound (snapping voice).Yet the principle of snap-fit joint has been described the closed mechanism of using best in the connection according to the two halves of putamina of the present invention.
According to closable joint of the present invention (being snap-fit joint) is one-way type (unidirectional type), and described one-way type is meant to be not intended to opens the junction surface.If afterwards for some reason, for example in order to check possible authentication information (identification information), and have to open the junction surface, then this will cause the damage at least to a certain extent of putamina structure inevitably.
According to a kind of embodiment, can on the first half closure edge and/or the second half closure edge, use and promote the bonded material of described two halves, for example be suitable for the binding agent of described application, be preferably the organosilicon binding agent.
Be when will be by closable joint closed, between described two halves, to form chamber (17) from what Fig. 1 b can obviously find out according to the putamina of Fig. 1 a.The first half hole, chamber (18) forms first side in chambeies (17), and the second half hole, chamber (19) forms second side in chambeies (17).The size and dimension in chamber (17) can be selected according to application.
Also can design, make in putamina, to form two or more chambeies putamina.For example, then can use this embodiment if wish in conjunction with several different activating agents in same implant inboard.
Under the situation in hole, two or more chambeies, the width of the closure edge of shell half is by limiting at the point of the ragged edge in the immediate hole of outward flange of position and described shell half and the distance between the outward flange.The point of the ragged edge in the immediate hole of outward flange of position and described shell half is meant the shortest point of outward flange distance described hole and described shell half.Under the situation in hole, a plurality of chamber, described partly do not have actual inward flange, but the width of closure edge limits as mentioned above.
Comprise the closure edge that extends to the zone of described half outward flange (13,15) from described half inward flange (14,16) and have certain design, make closable joint work by described two halves are connected to each other.The design that closure edge is carried out refer in particular to closure edge width (for example in the distance between described half inward flange and described half the outward flange), groove and projection design (for example cross section profile) and at horizontal and vertical upper groove and/or projection the position in the zone in closure edge (for example one that connect another and/or arranged side by side and successive/discontinuous).
According to a kind of embodiment, hole, described one or more chamber can only be arranged in half, and the inboard of second half closure edge is smooth thus.The width of the closure edge of half of hole does not limit according to half the width of closure edge as homologue (counterpart).Being arranged in different half holes also can be not in opposite directions, thus formation chamber in different half.
The hole, chamber can have Any shape, and for example it can be circular or oval-shaped.Also can ring-type arrange in described half the zone that closure edge limited by and/or two in one or more holes.
Must limit the degree of depth in hole, chamber, make that the mechanical endurance (mechanicaldurability) of implant in application is enough.The thickness of described shell half or must make that in the Zone Full of the distance between inner surface and the outer surface implant tolerates the required time and be not damaged (for example caving in) in application in described shell half.
According to the embodiment shown in Fig. 1 (this embodiment is most preferred embodiment with regard to the chamber), putamina comprises a chamber (17), and described chamber (17) are formed by the hole in opposite directions (18,19) of first half-sum the second half.
Fig. 2 illustrates putamina according to Fig. 1 before closure and sketch map afterwards.This figure also illustrates the film hinge.
Can freely select according to the shape of putamina of the present invention and design, this also is suitable for the outward appearance of the implant made thus.Must comprise the closable joint that is located substantially on edge and between the two halves of putamina, be used to place one or more one or more chambeies that contain the nuclear core of activating agent according to putamina of the present invention.The outward appearance of implant can be selected according to the object of treatment.Have columned design according to a preferred embodiment of the invention, make the horizontal cross-section of cylinder be basically circle (Fig. 1 a) or oval.The height of cylindric implant can be constant basically, perhaps its can be for example in edge than thin.According to the cylindric implant with oval cross section of the present invention can be especially in the end of ellipse than thin.
Implant also can contain the lobe (protruding part) with difformity and design, and described lobe for example is used for when implant is helped combination when the object for the treatment of removes.The shape of lobe and its position in implant can be selected based on the needs due to the application of the application target of lobe and/or implant.Lobe can be (handle-shaped) of handle-shaped for example, makes when removing implant, places the hole of handle and pull out implant under the help of described hook removing hook.Being used for the implant of long-term purposes, should avoid extra lobe, this is to form because described lobe may increase scar tissue.Main points with regard to the implant shape are that implant should be comfortable as much as possible in it is used.
The size of putamina, shape and wall thickness should make implant tolerate the required time in application.Life-span according to implant of the present invention can be several days or several thoughtful several years.Usually, the life-span is a some months to five year.Can be used for the subcutaneous sustained release of activating agent according to implant of the present invention the human and animal.
The overall dimension of design that putamina is carried out and corresponding implant can change based on application.Under applicable cases or at putamina closed and one or more nuclear cores that contain activating agent be in shell when inboard the overall diameter of implant can be preferably 5-20mm for for example 5-40mm, and most preferably it is 10mm.Particularly, the length of oval implant can be greater than 20mm, for example 40mm.The height of implant can be 1-10mm, and it is 1.5-5mm usually, and described height is preferably 2-3mm.Can be regarded as described design limiting factor be, the design closable joint, make described closable joint to finish and can use by injection molding technology by described two halves are connected to each other.
The surface area effect release rate of drugs of the thickness of membranous wall and shell also must be considered this point when the shape of determining shell and design.The surface geometry of the release area by for example improving activating agent such as the rate of release that fold, recess and handle influence the material that works in the manner known to persons skilled in the art.
Can change the composition of putamina by the PDMS elastomer of modification.For example, can influence the release of activating agent by described composition.For example, what can notice is, if putamina is made by fluorosilicone (for example trifluoro propyl replace siloxanes) or by the mixture manufacturing of fluorosilicone and PDMS, then the release of activating agent will be slowed down, and on the other hand, if the siloxanes manufacturing of putamina poly-by having (oxyalkylene) group or siloxanes of poly-by having (oxyalkylene) group and the mixture manufacturing of PDMS, then the release of medicine will speed up.
Except thickness, shape and the composition of putamina, also can control the release of medicine by the binding matrix (binding matrix) of medicine.
Described shell half (1,2) injection moulding or be injection molded into by film hinge (12) individually is connected to each other.After described two halves are connected, can remove the film hinge from implant.With regard to closable joint according to the present invention, described hinge makes the independently suitable connection of two halves maintenance, can easily realize closure thus.
Can make text will be replicated on the inner surface of shell by text is carved to mould, thereby during injection moulding, on the inner surface of putamina, produce the sign (for example authentication information) of hope.Also can after injection moulding, on the putamina inner surface, produce sign by for example laser.By these methods, can hide secret authentication information.
Can be before or after making described shell closure, preferably before making described shell closure, the nuclear core that contains activating agent of implant is bonded in the chamber (17).
Activating agent (its for example can be medicine) can be by combined in various manners in the inboard one or more chambeies that form of film.And the nuclear core that contains activating agent can be a matrix type, and perhaps activating agent may reside in the nuclear core and do not have any substrate.Therefore, the implant that contains according to closable joint of the present invention can be (the nuclear core comprises the rate of release of activating agent and putamina control activating agent) that mixes (rate of release of matrix core and putamina control activating agent) or the nuclear core pattern of type.In both cases, described one or more nuclear core should be filled in the inboard one or more chambeies that form of putamina basically.Preferably, the elasticity of membrane shell material (resilience) helps described nuclear core being full of the chamber.White space between described nuclear core and chamber is unfavorable for the diffusion of activating agent.
Can with activating agent for example with the PDMS elastomer-bonded, by being cross-linked to form the elastomeric sheet material of described PDMS (plate).Cut out disk (disc) and place the putamina inboard from described sheet material, and make the shell closure by snap-fit joint.Selectively, can be at first Polyethylene Glycol (PEG) be sprayed (inject) on the inner surface of putamina, then described disk is placed shell inboard and the shell closure.Polyethylene Glycol is injected in the contact that will improve on the inner surface of putamina between described nuclear core and the shell.
Contain activating agent and wait to place the nuclear core in the chamber of putamina to carry out injection moulding by the PDMS elastomer that is combined with medicine.After placing the nuclear core, by snap-fit joint with the shell closure.
Can medicine be combined with crystalline polyethylene glycol in room temperature.From described material molded sheet (piece) and place the putamina inboard.In case place in the body, PEG just will melt and change the diffusion of medicine.When being higher than normal body temperature, body temperature causes thawing by regulating the fusing point of PEG, can working as.
Also can be at room temperature injection and liquid macrogol or the bonded activating agent of silicone oil in the putamina of closure.
Independently putamina makes in containing the elastomer of medicine and can have the cross-linking system different with putamina.
Also activating agent can be pressed into sheet material with binding agent, cut out disk from described sheet material then.Described disk is placed chamber hole, and by snap-fit joint with the shell closure.In this embodiment, medicine binding matrix not.
Irrelevant with the number and the shape in chamber, above-mentioned being used to added and all can be expected in conjunction with all methods of activating agent.
Embodiment
Embodiment 1
The manufacturing of putamina:
The PDMS elastomer with injection moulding quality that will be divided into part A and part B, liquid silastic (LSR) mixes with 1: 1 volume ratio.Part A contains platinum catalyst and part B contains cross-linking agent, and crosslinkable elastomer is provided thus.Injection moulding LSR elastomer and allow at 115 ℃ crosslinked for example 5 minutes in mould.From mould, remove putamina then.
The manufacturing of drug core:
PDMS elastomer and medicine are for example mixed with 1: 1 weight rate.Described material uses hydraulic press 115 ℃ of compactings for example 5 minutes.Cut out disk/button (button) with punch press (hole press) from thin sheet material.
The assembling of implant:
The nuclear core disk that will contain medicine places one of two halves of putamina, and uses snap-fit joint with the shell closure toward each other by the inner surface that makes described two halves.After closed membrane shell, can with room temperature vulcanizing (room temperature vulcanising, RTV) the siloxanes binding agent is applied to closure edge.
Claims (10)
1. the putamina of implantable drug delivery system (3), it comprises the first half (1) and the second half (2), these two halves all comprise inner surface (5,7) and outer surface (4,6), it is characterized in that described two halves (1,2) be suitable for being connected to each other by closable joint, described closable joint be included on described the first half the inner surface (5) basically described the first half the closure edge (8) that is conitnuous forms of the periphery of described the first half inner surface (5) and on described the second half inner surface (7) basically in described the second half the closure edge (9) that is conitnuous forms of the periphery of described the second half inner surface (7), and the closure edge (8 of described two halves, 9) comprise at least one groove (10) that is continuous or discontinuous form and/or at least one projection (11) that is continuous or discontinuous form, and described putamina (3) is suitable for closure, makes at least one projection (11) of described the second half and/or at least one groove (10) offset by snap-fit joint and described the first half at least one groove (10) and/or at least one projection (11).
2. putamina as claimed in claim 1 (3) is characterized in that described the first half closure edge (8) comprises continuous recess (10), and described the second half closure edge (9) comprises successive projection (11).
3. putamina as claimed in claim 1 or 2 (3) is characterized in that described the first half (1) and described the second half (2) are connected to each other by film hinge (12).
4. any described putamina (3) in the claim as described above is characterized in that described putamina is by the polydimethylsiloxane manufacturing with injection moulding quality.
5. any described putamina (3) in the claim as described above, it is characterized in that described putamina be included in described the first half (1) and/or described the second half (2) inner surface (5,7) on basically described the first half (1) and/or the center of described the second half (2) inner surface (5,7) hole, chamber (18,19), make described the first half (1) and described the second half (2) hole, chamber (18,19) when with described putamina (3) closure, become in opposite directions.
6. any described putamina (3) in the claim as described above, it is characterized in that described putamina be included in described the first half (1) and/or described the second half (2) inner surface (5,7) on two or more holes, chambeies (18,19).
7. putamina as claimed in claim 6 (3), it is characterized in that described the first half (1) and described the second half (2) hole, chamber (18,19) when described putamina (3) is become in opposite directions when closed.
8. implant is characterized in that it comprises as any described putamina (3) in the claim 1 to 7 and nuclear core that at least one contains activating agent, and described nuclear core is suitable for being bonded at least one chamber (17) of described putamina inboard.
9. implant as claimed in claim 8 is characterized in that at least one nuclear core that has been shaped is suitable for placing at least one hole, chamber before with described shell closure by snap-fit joint.
10. implant as claimed in claim 8 is characterized in that described implant comprises the nuclear core of at least one injection at least one chamber of the putamina inboard of described closure.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FIU20070171 | 2007-04-27 | ||
| FI20070171U FI7960U1 (en) | 2007-04-27 | 2007-04-27 | Membrane shell for an implantable dosing system |
| PCT/FI2008/050217 WO2008132274A1 (en) | 2007-04-27 | 2008-04-23 | Membrane shell of an implantable dosage system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101686933A true CN101686933A (en) | 2010-03-31 |
| CN101686933B CN101686933B (en) | 2012-10-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008800224113A Expired - Fee Related CN101686933B (en) | 2007-04-27 | 2008-04-23 | Membrane shell of an implantable dosage system |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8152793B2 (en) |
| EP (1) | EP2139450A4 (en) |
| JP (1) | JP5406825B2 (en) |
| KR (1) | KR101461192B1 (en) |
| CN (1) | CN101686933B (en) |
| AU (1) | AU2008244162B2 (en) |
| BR (1) | BRPI0809806A2 (en) |
| CA (1) | CA2685467A1 (en) |
| EG (1) | EG25756A (en) |
| FI (1) | FI7960U1 (en) |
| HK (1) | HK1139874A1 (en) |
| IL (1) | IL201746A (en) |
| MX (1) | MX2009011539A (en) |
| RU (1) | RU2462233C2 (en) |
| WO (1) | WO2008132274A1 (en) |
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2007
- 2007-04-27 FI FI20070171U patent/FI7960U1/en not_active IP Right Cessation
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2008
- 2008-04-23 CN CN2008800224113A patent/CN101686933B/en not_active Expired - Fee Related
- 2008-04-23 MX MX2009011539A patent/MX2009011539A/en active IP Right Grant
- 2008-04-23 RU RU2009143915/15A patent/RU2462233C2/en not_active IP Right Cessation
- 2008-04-23 BR BRPI0809806-9A2A patent/BRPI0809806A2/en not_active IP Right Cessation
- 2008-04-23 WO PCT/FI2008/050217 patent/WO2008132274A1/en active Application Filing
- 2008-04-23 JP JP2010504771A patent/JP5406825B2/en not_active Expired - Fee Related
- 2008-04-23 AU AU2008244162A patent/AU2008244162B2/en not_active Ceased
- 2008-04-23 EP EP08761620A patent/EP2139450A4/en not_active Withdrawn
- 2008-04-23 KR KR1020097024615A patent/KR101461192B1/en not_active IP Right Cessation
- 2008-04-23 CA CA002685467A patent/CA2685467A1/en not_active Abandoned
- 2008-04-23 US US12/597,679 patent/US8152793B2/en not_active Expired - Fee Related
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- 2009-10-26 EG EG2009101588A patent/EG25756A/en active
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2010
- 2010-07-08 HK HK10106613.2A patent/HK1139874A1/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108030573A (en) * | 2017-12-15 | 2018-05-15 | 中国科学院深圳先进技术研究院 | Load complex stephanoporate bracket of drug bearing microsphere and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| IL201746A0 (en) | 2010-06-16 |
| CA2685467A1 (en) | 2008-11-06 |
| EG25756A (en) | 2012-06-26 |
| US8152793B2 (en) | 2012-04-10 |
| HK1139874A1 (en) | 2010-09-30 |
| US20100062034A1 (en) | 2010-03-11 |
| EP2139450A4 (en) | 2013-03-27 |
| BRPI0809806A2 (en) | 2014-10-07 |
| JP2010524615A (en) | 2010-07-22 |
| AU2008244162A1 (en) | 2008-11-06 |
| WO2008132274A1 (en) | 2008-11-06 |
| FIU20070171U0 (en) | 2007-04-27 |
| EP2139450A1 (en) | 2010-01-06 |
| FI7960U1 (en) | 2008-07-28 |
| RU2009143915A (en) | 2011-06-10 |
| KR20100017377A (en) | 2010-02-16 |
| CN101686933B (en) | 2012-10-24 |
| RU2462233C2 (en) | 2012-09-27 |
| AU2008244162B2 (en) | 2013-02-07 |
| MX2009011539A (en) | 2009-11-11 |
| JP5406825B2 (en) | 2014-02-05 |
| KR101461192B1 (en) | 2014-11-13 |
| IL201746A (en) | 2014-03-31 |
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